Drug Interactions between deserpidine and Promethazine VC Plain

MONITOR: Sympathomimetic amines may decrease the hypotensive effect of postganglionic adrenergic blocking agents, while the latter may potentiate the pharmacologic effects of direct-acting sympathomimetic amines (e.g., dobutamine, epinephrine, methoxamine, norepinephrine) but inhibit those that are primarily indirect-acting (e.g., mephentermine). Postganglionic adrenergic blocking agents such as guanadrel, guanethidine, and rauwolfia alkaloids work by depleting catecholamine stores from adrenergic nerve endings. Therefore, they may sensitize adrenergic receptors to direct-acting sympathomimetics, but blunt the effects of indirect-acting agents whose activity is mediated through the release of catecholamines. Guanethidine and reserpine have been reported to attenuate the pharmacologic effects (mydriasis, pressor response) induced by ephedrine and dopamine, both of which exhibit direct and indirect sympathomimetic activities (i.e., mixed-acting). However, guanethidine intensified the mydriasis produced by phenylephrine, which is also thought to be mixed-acting. Conversely, ephedrine has been shown to partially reverse the hypotensive effect of guanethidine.

MANAGEMENT: Due to their pressor effect, sympathomimetic amines should be used cautiously in patients with hypertension. Alternatives to postganglionic adrenergic blocking agents should be considered if patients are treated with sympathomimetic amines, since effects of the latter may be intensified or diminished depending on whether they are direct- or indirect-acting. Most agents with indirect sympathomimetic activity are mixed-acting, thus it may be difficult to predict how they will be affected by postganglionic adrenergic blocking agents. If the combination is used, blood pressure and heart rate should be monitored.

MONITOR: Phenothiazines, tricyclic antidepressants (TCAs), and some antipsychotic (neuroleptic) agents may potentiate the blood pressure lowering capabilities of other drugs with hypotensive effects due to their peripheral alpha-1 adrenergic blocking activity. Orthostatic hypotension and syncope associated with vasodilation may occur, particularly during initial dosing and/or parenteral administration of the phenothiazine, TCA, or neuroleptic. The severity of this interaction may be affected by the agent's affinity for the alpha-1 adrenoceptor. One in vitro study demonstrated an affinity for the alpha-1 adrenoceptor for some of these medications that was similar to, or greater than, those of alpha blocker medications used to treat hypertension. Examples of drugs evaluated in this study with a high affinity included amitriptyline, clomipramine, chlorpromazine, clozapine, doxepin, flupenthixol, lurasidone, nortriptyline, perphenazine, paliperidone, quetiapine, risperidone, sertindole, and ziprasidone. On the other hand, examples of those with lower affinities included aripiprazole, lofepramine, protriptyline, sulpiride, and amisulpride.

MANAGEMENT: Close clinical monitoring for development of hypotension is recommended if phenothiazines, tricyclic antidepressants (TCAs), or certain antipsychotic (neuroleptic) agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine, TCA, or neuroleptic may be appropriate, especially in the elderly. It may also be advisable to consider using a phenothiazine, TCA, or neuroleptic medication with a lower affinity for the alpha-1 adrenoceptor when possible. Patients should be counseled to avoid rising abruptly from a sitting or recumbent position and to notify their healthcare provider if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.